Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis.
BACKGROUND
A number of inflammatory and immune diseases are associated with vascular changes. Psoriasis, as an example, is a common inflammatory skin disease with dilation of capillaries as an early histological change. In more developed psoriatic lesions there is proliferation of blood vessels and neovascularization. The use of agents that target these vascular changes represents a novel therapeutic strategy in the treatment of inflammatory diseases. Since cartilage is an avascular tissue, it has been hypothesized that there may be factors found in cartilage that inhibit blood vessel formation.


OBJECTIVE
The objectives of this study were 1) to determine whether extracts of cartilage could inhibit angiogenesis, and 2) since altered angiogenesis is associated with certain diseases, including psoriasis, to examine whether inhibition of angiogenesis could potentially contribute to the treatment of psoriasis.


METHODS
Extracts of shark cartilage were prepared by homogenization and ultrafiltration to derive the active agent termed AE -941. This agent was tested for antiangiogenesis activity using the embryonic vascularization test, which is a modification of the ex vivo chick embryo culture (CAM). Since one of the first steps in angiogenesis is degradation by metalloproteinases of the basement membrane of capillaries, AE -941 was tested for collagenase activity using a fluorogenic peptide substrate. Anti-inflammatory properties were tested using a cutaneous irritation model in humans.


RESULTS
A dose dependent inhibition in embryonic neovascularization as well as in collagenase activity by AE -941 was demonstrated. When test compounds were applied on the forearms of test subjects, AE -941 was shown to have anti-inflammatory properties. Anecdotal data suggested that topical AE -941 had a beneficial effect in psoriasis.


CONCLUSIONS
Our results show that AE -941 has anti-angiogenic and anti-inflammatory properties. Antiangiogenesis agents such as AE -941 provide an entirely new class of agents to treat cutaneous and systemic diseases associated with altered vascularity.
Dupont
E
E
Les Laboratoires Aeterna, Ste-Foy, PQ, Canada.
Savard
P E
PE
Jourdain
C
C
Juneau
C
C
Thibodeau
A
A
Ross
N
N
Marenus
K
K
Maes
D H
DH
Pelletier
G
G
Sauder
D N
DN
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002356:Cartilage; D002478:Cells, Cultured; D002642:Chick Embryo; D017364:Collagenases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011565:Psoriasis / Q000188:drug therapy*; D012754:Sharks; D014020:Tissue Extracts / Q000494:pharmacology / Q000627:therapeutic use*
D014020:Tissue Extracts; C111481:shark cartilage extract; D017364:Collagenases